chr7-33216427-A-C

Variant names:

• chr7-33216427-A-C
• rs10262453
• NM_198428.3:c.442+38836A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_198428.3(BBS9):​c.442+38836A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.268 in 152,124 control chromosomes in the GnomAD database, including 6,164 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.27 (6164 hom., cov: 33)
• Consequence: BBS9 NM_198428.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.565
• Publications: 19 publications found

Genes affected

BBS9 (HGNC:30000): (Bardet-Biedl syndrome 9) This gene is downregulated by parathyroid hormone in osteoblastic cells, and therefore is thought to be involved in parathyroid hormone action in bones. The exact function of this gene has not yet been determined. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jan 2017]

BBS9 Gene-Disease associations (from GenCC):

• Bardet-Biedl syndrome 9

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• ciliopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• Bardet-Biedl syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.405 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198428.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BBS9	NM_198428.3	MANE Select	c.442+38836A>C		intron	N/A	NP_940820.1
	BBS9	NM_001348041.4		c.442+38836A>C		intron	N/A	NP_001334970.1
	BBS9	NM_001348036.1		c.442+38836A>C		intron	N/A	NP_001334965.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BBS9	ENST00000242067.11	TSL:1 MANE Select	c.442+38836A>C		intron	N/A	ENSP00000242067.6
	BBS9	ENST00000425508.6	TSL:1	c.307+38836A>C		intron	N/A	ENSP00000405151.2
	BBS9	ENST00000433714.5	TSL:1	n.442+38836A>C		intron	N/A	ENSP00000412159.1

Frequencies

GnomAD3 genomes AF: 0.268 AC: 40752 AN: 152006 Hom.: 6159 Cov.: 33

Gnomad AFR AF: 0.167

Gnomad AMI AF: 0.252

Gnomad AMR AF: 0.412

Gnomad ASJ AF: 0.245

Gnomad EAS AF: 0.0339

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.333

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.290

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.268 AC: 40765 AN: 152124 Hom.: 6164 Cov.: 33 AF XY: 0.273 AC XY: 20269 AN XY: 74366

African (AFR) AF: 0.167 AC: 6918 AN: 41510

American (AMR) AF: 0.413 AC: 6311 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.245 AC: 851 AN: 3468

East Asian (EAS) AF: 0.0342 AC: 177 AN: 5182

South Asian (SAS) AF: 0.216 AC: 1042 AN: 4818

European-Finnish (FIN) AF: 0.333 AC: 3527 AN: 10582

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.309 AC: 21020 AN: 67970

Other (OTH) AF: 0.287 AC: 604 AN: 2108

Alfa AF: 0.294 Hom.: 17711

Bravo AF: 0.270

Asia WGS AF: 0.135 AC: 470 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.6
DANN	Benign	0.78
PhyloP100		0.56
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10262453; hg19: chr7-33256039;